Calcium-Dependent Pulmonary Inflammation and Pharmacological Interventions and Mediators

Abstract

Pulmonary diseases present a significant burden worldwide and lead to severe morbidity and mortality. Lung inflammation caused by interactions with either viruses, bacteria or fungi is a prominent characteristic of many pulmonary diseases. Tobacco smoke and E-cig use (“vaping”) are considered major risk factors in the development of pulmonary disease as well as worsening disease prognosis. However, at present, relatively little is known about the mechanistic actions by which smoking and vaping may worsen the disease. One theory suggests that long-term vaping leads to Ca2+ signaling dysregulation. Ca2+ is an important secondary messenger in signal transduction. Cellular Ca2+ concentrations are mediated by a complex series of pumps, channels, transporters and exchangers that are responsible for triggering various intracellular processes such as cell death, proliferation and secretion. In this review, we provide a detailed understating of the complex series of components that mediate Ca2+ signaling and how their dysfunction may result in pulmonary disease. Furthermore, we summarize the recent literature investigating the negative effects of smoking and vaping on pulmonary disease, cell toxicity and Ca2+ signaling. Finally, we summarize Ca2+-mediated pharmacological interventions that could potentially lead to novel treatments for pulmonary diseases.

Serum YKL-40 Levels in Patients with Asthma or COPD: A Pilot Study

“…Since this protein is the precursor of calcitonin—a key hormone in calcium homeostasis [ 49 ]—these subjects are likely to exhibit altered calcium homeostasis. There is, indeed, growing evidence supporting the role of Ca 2+ signaling dysfunction in development/exacerbation of chronic respiratory diseases, as recently reviewed [ 50 ].…”

Vaping-Dependent Pulmonary Inflammation Is Ca2+ Mediated and Potentially Sex Specific

“…These lung diseases are characterized by lung inflammation, which is mediated by macrophages, neutrophils, and other immune cells that release chemical messengers known as cytokines and chemokines that modulate this inflammation [2,3]. This inflammation is present within one or both lungs and is typically caused by infection with viruses, bacteria, or fungal pathogens with prognosis known to worsen due to exposure to airway pollutants [4][5][6]. The societal intake of tobacco and the use of various smoking products such as electronic cigarettes (E-cigs, also known as "vaping") has been linked to worsened lung health and increasing susceptibility to infections, leading to these pulmonary diseases [7,8].…”

“…Calcium (Ca 2+ ) signaling dysregulation has been shown to play a pivotal role in inflammation and disease burden [6]. However, little is known about the mechanistic action of Ca 2+ signaling dysregulation and vaping.…”

“…Previous research on tobacco exposure has demonstrated that dysregulation in Ca 2+ signaling may be responsible for the adverse effects produced by smoking tobacco, with both increases [19] and decreases [20] in intracellular Ca 2+ concentrations being correlated with cell dysfunction and inflammation. E-cig use, which may have similar health implications as tobacco use, has garnered attention recently in studying its effects on pulmonary inflammation and Ca 2+ [6].…”